This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2014/064440 filed on Nov. 6, 2014, which claims priority to U.S. Application No. 61/900,915 filed on Nov. 6, 2013. The entire contents of each of the above-referenced disclosures are specifically incorporated herein by reference without disclaimer.
Oxygen is often employed to heal wounds (e.g., ulcers, abrasions, cuts, sores, etc.). Topical oxygen therapy calls for applying oxygen directly to an open wound. The oxygen dissolves in tissue fluids and improves the oxygen content of the intercellular fluids. Injuries and disorders which may be treated with topical oxygen include osteomylelitis, tendon and cartilage repair, sprains, fractures, burns and scalds, necrotizing fasciitis, pyoderma gangrenosum, refractory ulcers, diabetic foot ulcers and decubitus ulcers (bed sores) as well as cuts, abrasions, and surgically induced wounds or incisions.
Certain wounds and injuries can be treated using tissue-engineering scaffolds, which are porous sponge-like materials that can carry cells and other therapeutics that can slowly degrade or dissolve as it stimulates tissue formation. One problem with the use of tissue engineering scaffolds is that as the tissue grows within the scaffold, it reaches a point where it does not have enough oxygen supply to sustain growth before the tissue is adequately formed.
Several methods for oxygen generation for medical purposes have been described, but all with limitations. One study used angiogenic growth factors to promote vascularization in engineered tissue. However, the results did not indicate a faster rate of circulatory vessel growth; therefore, tissues were still limited in thickness (1: Smith et al., 2004). Another approach uses either dissolved oxygen in a topical cream, or glucose oxidase to capture and transport oxygen from the atmosphere to promote wound healing (4a: Davis, 2007). This approach was reported to only be able to deliver oxygen through about 600 microns of epidermis and dermis (4b,c: Roe, Berg et al., 2012; Roe, Ladininski et al., 2012), and is also limited to topical applications (4d: Roe, Gibbins et al., 2012).
A third approach utilizes decomposition of various inorganic peroxide compounds to generate oxygen. One makes use of calcium peroxide in a scaffold of paraffin (2: Oh et. al, 2008, p. 758). Similarly, Harrison et al. (8: Harrison et al., 2007) reported sodium percarbonate incorporated in films of Poly(d,l-lactide-co-glycolide) (PLGA) for in situ production of oxygen over a period of 24 h. When in contact with ischemic tissue, PLGA/percarbonate decreased tissue necrosis and cellular apoptosis in a mouse model. Still another system uses H2O2 microencapsulated in a PLGA shell that is embedded in an alginate matrix containing immobilized catalase to accelerate H2O2 decomposition to generate O2. This system was shown to provide an environment adequate for cells under a hypoxic environment and to increase cell survival (9: Abdi et al., 2011).
A fourth report investigated unicellular alga Chlorella as a natural photosynthetic oxygen generator (12:Bloch et al., 2006).
All of these approaches offer means of oxygen generation that can be used either internally or externally, but do not provide a means of recharging the oxygen reservoir. None of these approaches report the generation of singlet oxygen.
There remains a need for additional compositions and methods for supplying oxygenating materials for the treatment of wounds and the like.